Clinical Investigation
Whole-Pelvis Radiotherapy in Combination With Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High-Risk Prostate Cancer?

https://doi.org/10.1016/j.ijrobp.2009.02.069Get rights and content

Purpose

To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field.

Methods and Materials

From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of ≥20 ng/ml.

Results

With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results.

Conclusions

For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naïve patients, for whom a significant improvement in OS was observed.

Introduction

The role of whole-pelvis radiotherapy (WPRT) for high-risk prostate cancer is controversial 1, 2. Despite two prospective randomized trials, a uniform consensus has yet to be formulated for the appropriate use of WPRT 3, 4, 5. Compelling arguments can be made for and against its merit.

To date, the incremental benefit of WPRT has been marginal 3, 4, 5. Some proponents of dose escalation have duly argued that the available trials examining WPRT are limited by the low nominal doses delivered to the prostate. In fact, both of the aforementioned randomized studies used cumulative prostatic doses of only 66 to 70 Gy. On the basis of the contemporary dose escalation literature, these doses would now be considered suboptimal 6, 7, 8. It is logical to presume that without adequate treatment of the primary tumor, prophylactic treatment of the adjacent pelvic nodal basins is unlikely to offer maximal benefit. Conversely, with optimization of local therapy to the prostate, the potential benefit of regional nodal therapy might be fully exploited.

Interstitial brachytherapy is one of several strategies that has been used to optimize dose distribution in the setting of localized prostate cancer. Given the potential for local dose intensification and rapid radial falloff, brachytherapy advocates have long argued that this modality is ideally suited to address aggressive, clinically localized disease (9). While there is a significant amount of literature dedicated to the role of WPRT in conjunction with definitive external beam radiation therapy (EBRT), there is considerably less written about how WPRT should be incorporated into a brachytherapy treatment regimen. Brachytherapy has a proven track record in providing durable local and biochemical control of high-risk, organ-confined prostate cancer 10, 11, 12, 13, 14, 15. With the ability to provide local dose escalation, brachytherapy may be uniquely suited to reveal the potential benefits of treating subclinical, metastatic disease in the pelvic lymph nodes.

For over a decade, we have treated localized, high-risk prostate cancer with supplemental EBRT, followed by interstitial brachytherapy. In keeping with the D'Amico risk stratification system, we define high-risk prostate cancer as assessed at a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of >20 ng/ml (16). In the course of routine clinical practice, some of our high-risk patients have been treated with a mini-pelvis (MP) field, whereas others have received treatment with standard WPRT. Herein, we evaluate the impact of WPRT on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS), when given in combination with low-dose-rate brachytherapy implantation.

Section snippets

Methods and Materials

Between May 1995 and October 2005, 186 consecutive patients with a Gleason score of ≥8 and/or a PSA concentration of >20 ng/mL underwent permanent prostate brachytherapy in conjunction with supplemental EBRT by a single brachytherapist (GSM). All patients underwent brachytherapy more than 3 years prior to analysis, and no patient was lost to follow-up. Prior to the formulation of a treatment plan, all biopsy slides were reviewed by a single pathologist (EA). Preplanning technique,

Patient characteristics

The clinical and treatment-related parameters of the study population are summarized in Table 1. The median follow-up time for all patients was 6.7 years, with statistically longer follow-up with the MP cohort (p = 0.008). Among those patients treated with WPRT, there was a statistically higher preimplant PSA concentration (16.9 vs. 13.4 ng/ml, p = 0.046), percent risk of pelvic node involvement (16.3% vs. 12.2 %, p = 0.024 ng/ml), and a longer duration of ADT (15.2 vs. 7.8 months, p < 0.001).

Discussion

Roach et al.(3) were the first to evaluate the role of WPRT in a prospective, randomized fashion. In this landmark study, prostate cancer patients with an estimated risk of lymph node involvement of ≥15% were randomly assigned to one of four study arms: WPRT with neoadjuvant and concurrent hormonal therapy (WP plus NCHT), prostate-only radiotherapy with neoadjuvant and concurrent hormonal therapy (PO plus NCHT), WPRT with adjuvant hormonal therapy (WP plus AHT), or prostate-only radiotherapy

Conclusions

In high-risk prostate cancer patients treated with interstitial low-dose-rate brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS when it is given with WPRT. This trend is most apparent among ADT-naïve patients, in whom a significant improvement in OS was observed (p = 0.03). With optimal intraprostatic dose delivery, prophylactic treatment of the pelvic lymph nodes may prove beneficial. A prospective randomized study is needed to verify these findings.

References (25)

  • M. Roach

    Targeting pelvic lymph nodes in men with intermediate- and high-risk prostate cancer, and confusion about the results of the randomized trials

    J Clin Oncol

    (2008)
  • M. Roach et al.

    Phase III trial comparing whole-pelvic versus prostate only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413

    J Clin Oncol

    (2003)
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